Injectable and microporous scaffold of densely-packed, growth factor-encapsulating chitosan microgels

• Genipin-crosslinked chitosan microgels were produced in a single emulsion.
• Microgels encapsulated oppositely-charged growth factors and degraded with lysozyme.
• Microgels were condensed at pH 7.4 to form an injectable, shear-thinning scaffold.
• Endothelial cells migrated onto the microgels and within pores of the scaffold.
• This represents an ideal scaffold for minimally-invasive regenerative medicine.

In this work, an emulsion crosslinking method was developed to produce chitosan-genipin microgels which acted as an injectable and microporous scaffold. Chitosan was characterized with respect to pH by light scattering and aqueous titration. Microgels were characterized with swelling, light scattering, and rheometry of densely-packed microgel solutions. The results suggest that as chitosan becomes increasingly deprotonated above the pKa, repulsive forces diminish and intermolecular attractions cause pH-responsive chain aggregation; leading to microgel–microgel aggregation as well. The microgels with the most chitosan and least cross-linker showed the highest yield stress and a storage modulus of 16 kPa when condensed as a microgel paste at pH 7.4. Two oppositely-charged growth factors could be encapsulated into the microgels and endothelial cells were able to proliferate into the 3D microgel scaffold. This work motivates further research on the applications of the chitosan microgel scaffold as an injectable and microporous scaffold in regenerative medicine.